Two pathways for chromium(VI)-induced DNA damage in 14 day chick embryos: Cr-DNA binding in liver and 8-oxo-2'-deoxyguanosine in red blood cells.
Two pathways for chromium(VI)-induced DNA damage in 14 day chick embryos: Cr-DNA binding in liver and 8-oxo-2'-deoxyguanosine in red blood cells.
复制标题
14 天鸡胚中铬 (VI) 诱导的 DNA 损伤有两种途径：肝脏中的 Cr-DNA 结合和红细胞中的 8-oxo-2-脱氧鸟苷。
DOI：
10.1093/carcin/15.12.2911
复制
发表时间：
1994
期刊：
影响因子：
4.7
通讯作者：
Wetterhahn,KE
中科院分区：
文献类型：
--
作者：
Misra,M;Alcedo,JA;Wetterhahn,KE
先前的研究表明，铬(VI)在14日龄雏鸡胚胎中诱导细胞特异性DNA损伤，即肝脏DNA交联和红细胞DNA链断裂。本文研究了铬(VI)对14日龄雏鸡肝脏和红细胞DNA损伤的直接途径和间接途径。肝组织铬-DNA结合量呈剂量依赖性增加。红细胞中的铬-DNA结合量比肝脏低10倍，尽管红细胞对铬的摄取量只比肝脏低2倍。红细胞中8-oxo-DG的生成水平在所有铬(VI)剂量下都有所增加，但在0.10 mmolCr(VI)/kg时达到峰值，而在肝脏中8-oxo-DG的生成水平并未高于本底水平。用L-丁硫宁-R、S-亚磺胺耗竭谷胱甘肽，研究了谷胱甘肽在铬(VI)诱导的细胞DNA损伤中的作用。在BSO存在或不存在的情况下，用铬(VI)处理的胚胎的肝脏和红细胞中的谷胱甘肽水平没有变化。0.050和0.10mmolCr(VI)/kg组胚胎肝脏铬摄取量略有增加，但0.20mmolCr(VI)/kg组肝铬吸收率无明显变化。BSO对红细胞摄取铬无明显影响。谷胱甘肽的去除对铬(VT)处理的胚胎的肝脏和红细胞的铬-DNA结合没有影响。然而，在所测试的所有剂量的铬(VI)中，谷胱甘肽的耗竭显著降低了红细胞中8-oxo-DG的水平。在BSO存在或不存在的情况下，铬(VI)处理的胚胎肝脏中8-oxo-DG的水平保持在背景水平。这些结果表明，铬(VI)对14日龄雏鸡胚胎的DNA损伤是通过铬与肝脏DNA的直接相互作用，而是通过间接的红细胞氧化途径。这表明谷胱甘肽在铬(VI)诱导的红细胞中8-oxo-DG的形成中起重要作用。
Previous studies have shown that chromium(VI) induced cell-specific types of DNA damage, i.e. DNA cross-links in liver and DNA strand breaks in red blood cells, in 14 day chick embryos. Direct and indirect pathways for chromium(VI)-mediated DNA damage, in the form of Cr-DNA binding and 8-oxo-2’-deoxyguanosine (8-oxo-dG) respectively, were examined in liver and red blood cells of 14 day chick embryos. Levels of hepatic Cr-DNA binding increased in a Cr(VI) dose-dependent manner. Cr-DNA binding in red blood cells was 10-fold lower than in liver, although the Cr-uptake in red blood cells was only 2-fold lower than in liver. The level of 8-oxo-dG formation in red blood cells increased at all Cr(VI) doses tested but peaked at 0.10 mmol Cr(VI)/kg, whereas no increase hi 8- oxo-dG levels over background levels was observed in liver of Cr(VI)-treated embryos. The possible role of glutathione hi modulating Cr(VI)-induced DNA damage was examined by using L-buthionine-R,S-sulfoximine (BSO) to deplete glutathione. No changes in glutathione levels were observed in either liver or red blood cells of embryos treated with Cr(VI) in the presence or absence of BSO pretreatment Ascorbate levels in liver and red blood cells were not affected by treatment of embryos with chromium(VI), BSO or Cr(VI) and BSO. Depletion of glutathione by BSO resulted in a small increase of chromium uptake in liver of embryos treated with 0.050 and 0.10 mmol Cr(VI)/kg, but had no effect on hepatic chromium uptake at 0.20 mmol Cr(VI)/kg. BSO had no effect on chromium uptake in red blood cells. Depletion of glutathione had no effect on hepatic or red blood cells Cr-DNA binding in embryos treated with Cr(VT). However, depletion of glutathione significantly decreased the 8-oxo-dG levels in red blood cells at all Cr(VI) doses tested. Levels of 8-oxo-dG in liver of Cr(VI)-treated embryos remained at background in the presence or absence of BSO pretreatment These results indicate that Cr(VI)-induced DNA damage in 14 day chick embryos is through a direct interaction of chromium with DNA in liver, but is through an indirect oxidative pathway in red blood cells. It appears that glutathione plays an important role in chromium(VI)-induced formation of 8-oxo-dG in red blood cells.